title: α1-adrenoceptor activation induces phosphorylation of β2-adrenoceptors in human prostate tissue.
abstract: OBJECTIVE
  • To test whether β1-adrenoceptor activation leads to phosphorylation of the β2-adrenoceptor in human prostate tissue.
  
  
  METHODS
  • Prostate tissue from patients undergoing radical prostatectomy was stimulated in vitro with the α1-adrenergic agonist phenylephrine (10 µM). • α2-adrenoceptor phosphorylation at serines 345/346 was studied using Western blot analysis with a phospho-specific antibody. • The role of second messenger kinases was assessed by studying the effects of the protein kinase C (PKC) inhibitor Ro 31-8425 and the protein kinase A (PKA) inhibitor H89 on phenylephrine-induced phosphorylation. • The expression of G protein-coupled receptor kinases (GRKs) 2/3 was analysed using quantitative reverse-transcriptase-polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemistry.
  
  
  RESULTS
  • Stimulation of prostate tissue with phenylephrine resulted in phosphorylation of the β2-adrenoceptor (5, 10 and 20 min after stimulation). • This α1-adrenoceptor-induced phosphorylation of β2-adrenoceptors was resistant to inhibition of PKC and PKA. • Changes in phosphorylation levels were not attributable to changes in receptor levels, as these remained constant during stimulation. • RT-PCR and Western blot analysis showed expression of GRK2/3 in human prostate tissues. • Immunohistochemical staining showed that GRK2/3 expression in human prostate tissue is located to stromal and smooth muscle cells.
  
  
  CONCLUSIONS
  • Activation of α1-adrenoceptors causes phosphorylation of β2-adrenoceptors in the human prostate. This may enhance α1-adrenergic contraction and is possibly mediated by GRK2, which is expressed in prostate smooth muscle. • Mutual regulation between different adrenergic receptors might be involved in the therapeutic effects of α1-blockers in patients with benign prostate hyperplasia.
authors.affiliation: Department of Urology, University of Munich, Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hennenberg
authors.forename: Frank
authors.initials: F
authors.lastname: Strittmatter
authors.forename: Sebastian
authors.initials: S
authors.lastname: Walther
authors.forename: Petter
authors.initials: P
authors.lastname: Hedlund
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
authors.forename: Christian G
authors.initials: CG
authors.lastname: Stief
authors.forename: Boris
authors.initials: B
authors.lastname: Schlenker
authors.forename: Christian
authors.initials: C
authors.lastname: Gratzke
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists; D051606:G-Protein-Coupled Receptor Kinase 1 / Q000378:metabolism; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D000318:Adrenergic beta-Agonists; D007211:Indoles; D007546:Isoquinolines; D008301:Maleimides; D047428:Protein Kinase Inhibitors; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D013449:Sulfonamides; C071924:Ro 31-8425; D010656:Phenylephrine; D051606:G-Protein-Coupled Receptor Kinase 1; C496764:GRK1 protein, human; C496567:GRK2 protein, human; D054769:G-Protein-Coupled Receptor Kinase 2; D019204:GTP-Binding Proteins; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide